Clinical trials

The goal of this clinical trial is to determine whether a selected population of women with early-stage, low-risk breast cancer can avoid hormone therapy without increasing their risk of relapse. It will also evaluate the prognosis of these participants compared to participants who received standard treatment with hormone therapy in another study, estimate the risk of specific recurrence, cardiovascular and bone health, and participants' quality of life. All participants will have undergone surgery and possibly radiation therapy, but unlike standard care, they will not receive hormone therapy afterward. Participants will be enrolled for two years and followed for up to five years after the last participant is enrolled in the trial to monitor for long-term cancer recurrence.

At the time of diagnosis, 25% of patients with colorectal cancer present with liver metastasis (CRLM). Among patients with localized colorectal cancer (Stages I-III), 50% to 70% will develop liver metastases during the course of their disease. Surgery in combination with intravenous (IV) chemotherapy represents the only chance of cure for selected patients by removing all liver metastases and treat residual microscopic disease by postoperative chemotherapy for 3 months. However, up to two-thirds of patients will experience a relapse, with about two-thirds of recurrences occurring in the liver. Hepatic arterial infusion (HAI) chemotherapy has been proposed to improve the efficacy of chemotherapy by increasing the concentration of the drug in the liver. This treatment is currently administered by infusion through a specific catheter placed in the artery feeding the liver parenchyma, connected to a subcutaneous port-a-cath system. Several trials have shown that the administration of floxuridine or oxaliplatin via HAI combined with IV chemotherapy achieves a higher response rate compared to IV chemotherapy alone in patients with unresectable colorectal liver metastases. HAI chemotherapy has thus become an attractive therapeutic option for patients who underwent curative-intent surgery to reduce the risk of hepatic recurrence. The investigators recently demonstrated in the PACHA-01 phase II randomized study a 47% decrease of hepatic recurrence risk by HAI of oxaliplatin compared to IV chemotherapy alone, despite a higher but manageable toxicity among 99 patients who underwent curative surgery considered at high risk of recurrence. Moreover, this study showed promising results in terms of time to recurrence and survival. Moreover, feasibility has improved in recent years with the development of non-invasive techniques for HAI. The investigators propose to conduct the PACHA-02 trial to evaluate the efficacy in terms of disease-free survival of oxaliplatin administered via HAI in combination with IV chemotherapy after curative resection in patients with colorectal cancer at high risk of recurrence. A total of 272 patients who will undergo curative surgery for at least 4 CRLM with no residual disease on imaging performed within 4 weeks after surgery will be included. Patients will then be randomized to receive oxaliplatin-based chemotherapy either via HAI or IV combined with standard IV chemotherapy, every 2 weeks for at least 3 months. The primary objective of this study will be to determine if the administration of oxaliplatin via HAI increases the time between treatment and disease recurrence compared to IV administration. The secondary objectives include overall survival, hepatic recurrence-free survival, safety, pattern of recurrence, and quality of life.

The advent of CDK4/6 inhibitors (drugs designed to block the action of CDK4/6 proteins, which play a key role in cell proliferation) has improved treatment prospects for patients with metastatic breast cancer whose tumour cells express hormone receptors but not the HER2 protein (HR+/HER2-). The NATALEE study showed that the addition of ribociclib for three years to conventional adjuvant hormone therapy (i.e. after surgery) prolonged survival free of invasive disease (i.e. extending to surrounding tissues) in patients with early HR breast cancer+ /HER2-. Unlike other studies, NATALEE included a group of patients at intermediate risk of recurrence, usually treated with adjuvant chemotherapy before receiving hormone therapy. However, the benefit of adjuvant chemotherapy in these patients is uncertain. The hypothesis of the NoLEEta study is that by using the CDK 4/6 inhibitor, patients could avoid adjuvant chemotherapy and therefore be spared the side-effects associated with this chemotherapy, without reducing the efficacy of the treatment.

The objective of our study is to demonstrate that it is possible to detect and treat human papilloma virus (HPV)-related oropharyngeal cancers (OPC) early using simple blood tests. The success of this strategy will be evaluated by the number of participants positive for both HPV16-E6 serology and HPV circulating tumor DNA (ctDNA) whose early management has allowed the detection of a cancerous lesion and/or whose HPV ctDNA results have normalized after surgical intervention. If this study is conclusive, it could pave the way for the implementation of a national screening strategy for HPV-related OPC.

This database compiles data from existing data available from patient's electronic medical records (EMR) at the 38 participating hospitals (20 French comprehensive cancer centers and 18 public hospitals).

The Epidemiological Strategy and Medical Economic (ESME) Breast cancer Database is a multicenter real life database using a retrospective data collection process across 18 French comprehensive cancer centers (FCCC) spread over 20 sites. This database compiles data from patient's electronic medical records (EMR).

The goal of this clinical trial is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of PFS. The main questions it aims to answer are: Does FOLFIRI + ivonescimab improve progression-free survival compared to FOLFIRI + bevacizumab? Participants will: Take FOLFIRI + ivonescimab or FOLFIRI + bevacizumab every 2 weeks for a maximum of 24 months Visit the clinic once every 2 weeks for checkups and tests, and have imaging done every 8 weeks Complete some quality of life questionnaires every 8 weeks

Although treatments for breast cancer have improved, 20-30% of patients with early disease develop metastases (cancer that spreads to other parts of the body). Among the different types of breast cancer, hormone-sensitive cancers that do not overexpress the HER2 protein (HR+/HER2-) are the most common. For patients with this type of cancer, an endocrine treatment such as aromatase inhibitors, tamoxifen or fulvestrant, is often used and may be combined with drugs called CDK4/6 inhibitors, which help improve survival rate. However, when the cancer becomes resistant to these treatments, treatment strategies are more limited A new drug, prifetrastat (PF-07248144), which targets KAT6 proteins, which play a role in the growth of cancer cells, has shown promising results. Indeed, associated with fulvestrant, it allowed to fight against cancer in some patients who had already received many treatments. The UNLOCK-EPIBREAST study aims to investigate whether the combination of prifetrastat plus fulvestrant could offer a new therapeutic option for people with HR+/HER2- metastatic breast cancer who have already received endocrine therapy plus CDK4/6 inhibitors.

Radiotherapy after breast cancer surgery can lead to side effects like arm lymphedema (arm swelling). Lymphedema can cause long-term discomfort and affect quality of life. The goal of this clinical investigation is to determine whether using an artificial intelligence (AI) tool to predict the risk of developing arm lymphedema after breast cancer radiotherapy can help patients and physicians make better treatment decisions. This AI tool has been developed to determine each patient's personalized risk of developing lymphedema. The risk is shown using a web app that explains the factors involved and offers suggestions like using a compression sleeve to reduce the risk. Women (≥18 years) with breast cancer (cT1-4, cN0-N3, M0) requiring regional lymph node irradiation post-mastectomy or breast-conserving surgery are eligible, regardless of hormone receptor status, tumor grade, or HER2 status. Patients will be randomly divided into two groups: * Experimental group: Patients and physicians will see the AI-predicted risk and use it to guide treatment choices. * Control group: The risk is not shown. The radiotherapy treatment will be exactly the same as the treatment that you would have received if you had not taken part in this clinical investigation. The only intervention will be whether or not the risk you are informed of the risk of developing lymphedema. All patients will be followed for two years to monitor: * How risk communication influences radiotherapy treatment choices * The occurrence of side effects * The predictive performance of the AI tool * Patients' quality of life * Compliance with compression sleeve use * Loco-regional recurrence-free survival, distant disease-free survival, and overall survival

The object of this trial is to test whether ivonescimab is superior to standard chemotherapy (FOLFOX regimen) for the treatment of patients with advanced biliary tract cancer after failure of a first line of chemotherapy. It is only open to patients who participated in the SAFIR-ABC10 trial (NCT05615818) but did not receive experimental treatment. Eligible patients will be randomised (2:1) to receive either ivonescimab or FOLFOX. Treatment will be continued until disease progression, or a maximum of 34 cycles of ivonescimab (experimental arm), whichever occurs first.

The object of this trial is to evaluate whether the introduction of a targeted therapy after 4 cycles of the current standard-of-care treatment for advanced biliary cancer is superior to continuing with the standard treatment. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a molecular profile of the patient's tumour will be obtained, and (ii) a randomised comparative trial in which patients with disease control after 4 cycles of standard treatment, and whose tumour harbours a targetable molecular alteration, will be randomised (2:1) to receive either a matched targeted therapy or to continue with the standard treatment.

The goal of this clinical trial is to evaluate the addition of ivonescimab to standard chemotherapy in patients with advanced or metastatic gastric and gastroesophageal adenocarcinoma. The main question it aims to answer is : Does the addition of ivonescimab increase the response to treatment ? Participants will visit the clinic every 2 weeks for checkups, treatment administration and tests for collection of adverse events.

The goal of this clinical trial is to establish guidelines for fluoropyrimidine dose reduction according to uracilemia in patients with DPD deficiency in the treatment of digestive cancers. The main question it aims to answer is: \- Which reduction dose of fluoropyrimidine is needed for patient with DPD deficiency? Participants will: * Take the treatment with the reduction of dose stated by the protocol * Visit the clinic once every 2-3 weeks for checkups and tests for collection of adverse events

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors.

Oropharyngeal cancer (OPC) is the most common type of head and neck cancer. The current standard treatment for this cancer is radiotherapy (RT) of the tumour and lymph nodes of both sides of the neck, combined with concurrent chemotherapy for advanced stages. Even though a small proportion of patients with this cancer have involvement of the lymph nodes of the neck on the opposite side of the tumour (contralateral involvement) or involvement of the lymph nodes on both sides of the neck (bilateral involvement), bilateral radiotherapy is performed due to the risk of contralateral microscopic involvement, which is invisible on imaging and clinical examination. Bilateral radiotherapy causes more adverse events, leading to a decrease in quality of life. Lymphatic mapping using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging is a technique that visualises the lymphatic drainage of the tumour and thus determines whether radiotherapy should be delivered unilaterally or bilaterally to the lymph nodes. This technique would therefore reduce adverse events and improve quality of life, while maintaining the efficacy of radiotherapy. The goal of the clinical trial SELECT-FR is to investigate if the efficacy of a lymphatic drainage mapping with a SPECT-CT-guided approach is acceptable in terms of two-year Disease Free Survival (DFS) rate in patients with lateralized OPC.

Rationale: Around 70 to 80% of breast cancers are so-called "hormone-dependent" (HR+)/HER2-. For more than 50 years, studies have shown that chemotherapy and optimised hormonal treatments (hormone therapy), including a drug associated with ovarian suppression (OFS), improve survival in patients with these cancers, which are characterised by a high risk of relapse. However, younger patients suffer more side effects than older women, particularly from chemotherapy. This can affect their quality of life and reduce their ability to work. For post-menopausal women, genetic tests exist to assess whether chemotherapy is really necessary in addition to hormonal treatment. However, for high-risk premenopausal patients, chemotherapy is still systematically recommended, as no study has proved that it can be safely avoided. Clinical trials based on risk stratification using genetic tests have not been conclusive, but the majority of premenopausal women included had not received optimal hormone treatment. It is possible that the beneficial effect of chemotherapy is partly due to the artificial menopause it induces. Some experts believe that, for patients with a high clinical risk but a low genetic risk, an optimised hormonal treatment (drug + OFS) could suffice, without the need for chemotherapy. Objectives: Main objective: The aim of the study is to determine whether the use of a genetic test (Prosigna®) to decide whether or not to administer chemotherapy produces results as good as standard treatment (systematic chemotherapy) in premenopausal women with hormone-dependent (HR+) breast cancer/HER2-, by assessing their risk of cancer recurrence. The secondary objectives include verifying whether, in patients with a low Prosigna® score (around 70% of cases), optimised hormonal treatment (including suppression of ovarian function) is as effective as chemotherapy combined with hormonal in treatment preventing cancer recurrence. The study also seeks to compare the efficacy of treatment Prosigna®-guided versus systematic chemotherapy in terms of recurrence and quality of life, as well as economic aspects. Finally, the aim is to understand patients' concerns about the concept of reducing treatment (therapeutic de-escalation) and the way in which this information is communicated to them. The primary endpoint of the study is to measure the time elapsed between the start of participation in the study and the appearance of an event indicating a return of the cancer. This includes the return of cancer in the same breast or neighbouring areas, the spread of cancer to other parts of the body, the appearance of new cancer in the other breast or death from any cause. Trial Population: The study includes women major premenopausal diagnosed with invasive, hormone receptor-positive (ER+) and HER2-negative breast cancer. Patients must have undergone breast and axillary surgery recent and have a tumour sample suitable for analysis by the testProsigna® . They must be able to receive the study treatments Postmenopausal women, women with stage IV breast cancer, women who have already received adjuvant systemic treatment (except short neoadjuvant hormone therapy), women with a recent history of invasive cancer, pregnant women or women who are breast-feeding will not be able to take part in the study. Interventions: After agreeing to take part, patients will enter the pre-inclusion period (up to 28 days before randomisation), during which the investigator will carry out all the necessary tests to assess their eligibility. The investigator will then randomise the patients to find out which treatment they have been assigned, no more than 2 weeks later: the experimental group will receive a treatment decided on the basis of the results of a genomic test: either chemotherapy and hormone therapy, or hormone therapy alone. The control group will receive the standard treatment. The treatment and follow-up phases are the same as for standard care. Information on the quality of life patient's will and other information (associated costs, perception of their participation in the study, etc.) also be collected by means of questionnaires completed by the patients during the 5 years following randomisation.

Breast cancer remains the most common cancer among women and a major cause of death despite advances in screening and treatment. Current screening programs are not personalized and are experiencing declining participation. A promising strategy for breast cancer control would be to implement risk-based prevention and early screening, targeting individuals at high risk of developing breast cancer, in order to improve chances of cure and reduce the need for more intensive treatments. The MyPeBS study was designed to assess whether personalized breast cancer screening (based on an individual's risk of developing breast cancer) is as effective as, or more effective than, current standard screening. Lifestyle interventions involving changes in diet or physical activity, for example, have been shown to be effective in reducing the risk of developing breast cancer, whether low or high. The MyPeBS study evaluates personalized screening but offers limited information on breast cancer prevention. MyPREV is a project that aims to assess the feasibility and impact of a personalized online program on breast cancer risk reduction measures. This program is offered to women at high risk of developing breast cancer as part of the European MyPeBS screening study. The main objective is to evaluate adherence to a personalized, online breast cancer prevention program focused on lifestyle and its acceptance among women at high or very high risk of developing cancer who participated in the MyPeBS study.

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab. The main questions it aims to answer are: * Does the addition of Mitazalimab enhance efficacy? * What medical problems do participants have when taking Mitazalimab + mFOLFOX? Participants will: * Take drug mFOLFOX every two weeks until disease progression or mFOLFOX every two weeks plus mitazalimab in addition to mFOLFOX, with a first injection 7 days before the first mFOLFOX chemotherapy and then 3 days after the start of each mFOLFOX cycle. * Visit the clinic once every 2 weeks for checkups and tests * Have a radiological assessment every 8 weeks during treatment. After stopping treatment, participants will be monitored at the hospital every 8 weeks if no progression is observed, or every 12 weeks after disease progression.

Over the past decade, cancer immunotherapy has profoundly transformed oncology by harnessing the patient's immune system to target tumors. These therapies have demonstrated the potential for durable responses and, in some cases, long-term remission or cure. However, despite these advances, only approximately 20-30% of patients derive significant clinical benefit from current immunotherapies. In parallel, investment in oncology drug development continues to grow, with global spending projected to reach $307 billion by 2026. Yet, the overall failure rate in oncology drug development remains extremely high, at around 95%, highlighting a critical gap between scientific innovation and clinical success. One major contributor to these failures lies in traditional drug development and regulatory paradigms, which have historically relied on cancer histology as the primary framework for patient selection and treatment evaluation. This approach is based on the flawed assumption that tumors of the same histological type share similar biological behavior and therapeutic vulnerabilities, and that localized and advanced disease are biologically comparable. In reality, tumor biology-rather than histology-plays a decisive role in determining immunotherapy efficacy. Substantial heterogeneity exists within the same cancer type, leading to widely variable patient outcomes even among individuals receiving identical treatments. The recent emergence of tumor-agnostic approvals for immunotherapies has reinforced the importance of shared biological features across cancer types. Approvals of anti-PD-1 therapies for microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), or tumor mutational burden-high (TMB-H) cancers have demonstrated that biological characteristics can transcend tissue of origin. However, the predictive value of current companion diagnostic assays remains limited. Only 30-40% of biomarker-positive patients respond to treatment, underscoring the inadequacy of existing patient selection strategies. These limitations are partly driven by the methodologies used in industry-sponsored clinical trials, which typically rely on tumor samples processed by contract research organizations (CROs). For logistical reasons, analyses are performed on formalin-fixed paraffin-embedded (FFPE) or frozen tissues using conventional techniques such as immunohistochemistry (IHC) and DNA/RNA sequencing. While informative, these methods are often slow, complex, and insufficiently sensitive or specific to guide timely treatment decisions, particularly when results are required within the 3-4 week window following trial consent. Moreover, they offer limited insight into dynamic parameters such as target expression, saturation, and engagement during treatment. There is therefore a pressing need for innovative oncology drug development strategies that prioritize biologically driven patient selection, support tumor-agnostic approaches, and enable truly personalized cancer therapy. Addressing this need requires technologies capable of rapid, comprehensive, and functional immune and tumor profiling. METAREM is part of the broader REMISSION program, which aims to improve treatment stratification and generate early clinical evidence to support the development of novel therapies and patient selection strategies. METAREM is a master protocol designed to test innovative treatment approaches through dedicated sub-protocols in patients with unresectable locally advanced or metastatic cancers. All patients enrolled in METAREM undergo in-depth immuno-biological characterization at both tumor and blood levels using the PORTRAIT immunoprofiling platform. PORTRAIT analysis is performed on fresh whole blood and fresh tumor biopsies, enabling rapid, sensitive, and highly specific profiling of each patient's immune and tumor biology. This real-time approach overcomes the limitations of conventional tissue-based assays and allows for a comprehensive understanding of disease mechanisms at the individual level. By integrating these data, METAREM aims to stratify patients into the most appropriate therapeutic sub-protocols, thereby advancing personalized cancer treatment and supporting more efficient, biology-driven drug development.

Anti-PD-1 monotherapy has demonstrated significant clinical efficacy in advanced or metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression (tumor proportion score \[TPS\] \>50%), outperforming platinum-based chemotherapy in terms of objective response rate (ORR) and overall survival (OS). Pivotal randomized trials such as KEYNOTE-024 and EMPOWER-Lung 1 established the superiority of PD-1 blockade in this patient population, leading to regulatory approvals by both the FDA and EMA for first-line treatment. These studies confirmed that a subset of patients can achieve deep and durable responses with immunotherapy alone, highlighting the potential of immune checkpoint inhibition to provide long-term clinical benefit without the toxicities associated with cytotoxic chemotherapy. Despite these successes, accumulating clinical evidence has revealed a clinically significant risk of hyperprogressive disease (HPD) in a subset of patients treated with anti-PD-1 monotherapy. HPD is characterized by an unexpected and rapid acceleration of tumor growth following treatment initiation and is associated with early clinical deterioration and increased mortality. This phenomenon likely contributes to the early crossover of survival curves frequently observed when comparing immunotherapy alone with chemotherapy in first-line NSCLC trials. In contrast, such early survival crossover is not observed in trials comparing chemotherapy-immunotherapy combinations with chemotherapy alone, including CheckMate-227, CheckMate-9LA, KEYNOTE-189, and KEYNOTE-407. These results have led many thoracic oncologists to favor combined chemo-immunotherapy regimens as first-line treatment, as they reduce the risk of HPD and increase initial ORR. However, while chemotherapy combined with immunotherapy effectively mitigates the risk of hyperprogression and improves early response rates, it also appears to compromise the durability of antitumor immune responses. Clinical data indicate that the median duration of response with chemo-immunotherapy combinations is approximately 10-11 months, compared with more than 22 months for anti-PD-1 monotherapy alone. This difference is likely attributable to the cytotoxic effects of chemotherapy on immune effector cells, which may limit the persistence and depth of immune-mediated tumor control. Consequently, there remains a strong clinical need to identify patients who could safely and effectively benefit from anti-PD-1 monotherapy while avoiding unnecessary exposure to chemotherapy. Multiple early-phase translational studies have independently identified soluble plasma biomarkers associated with response or resistance to PD-1 blockade in advanced NSCLC. Building on this body of evidence, translational analyses conducted at Gustave Roussy Cancer Center have identified a composite signature of circulating soluble factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD14 (sCD14), soluble CD25 (sCD25), and growth differentiation factor-15 (GDF-15). Together, these biomarkers define a Pro-Tumoral Inflammation (PTI) signature that is strongly associated with primary resistance to anti-PD-1 monotherapy. Elevated PTI scores reflect a systemic inflammatory state that promotes tumor progression and immune dysfunction, and have been linked to poor clinical outcomes, including non-response and hyperprogressive disease. Within the META-1 sub-protocol of the METAREM master protocol, the investigators propose to integrate these soluble biomarkers into a single PTI score generated through baseline PORTRAIT immunoprofiling. The primary objective of this approach is to prospectively validate the predictive value of the PTI score for anti-PD-1 monotherapy efficacy in advanced NSCLC. By enabling early identification of patients at high risk of resistance or hyperprogression, this strategy aims to refine patient stratification and guide first-line treatment selection. Ultimately, the use of the PTI score could allow clinicians to identify patients most likely to benefit from anti-PD-1 monotherapy, preserving the potential for durable responses while sparing others from ineffective treatment and optimizing the overall therapeutic strategy in advanced NSCLC.

The success of anti-PD-1 and anti-CTLA-4 therapies has initiated a paradigm shift in oncology, with drugs now targeting the immune system rather than cancer cells to stimulate the antitumor immune response. Intratumoral (IT) delivery of immunostimulating agents reduces the systemic toxicity associated with monoclonal antibodies (mAbs) targeting immune checkpoints. Notably, IT injections of immune checkpoint blockade (ICB) have been shown to induce immune-mediated tumor responses both at the injected site and at distant, non-injected tumor sites. While surgery has traditionally been the preferred treatment for stage III and IV melanoma patients, neoadjuvant therapy with anti-CTLA-4 and anti-PD-1 agents has shown promising efficacy. In patients with localized melanoma, it is hypothesized that IT administration of ipilimumab (anti-CTLA-4 Ab) combined with nivolumab (anti-PD-1 Ab) will provide the most effective and safe treatment combination. The NEO-1 study is a proof-of-concept clinical trial designed as a sub-protocol of NEOREM master protocol (NCT07262489) to validate the intratumoral immunotherapy approach, aiming to maximize the dose/efficacy ratio of combined ipilimumab and nivolumab treatment while minimizing systemic adverse events. This is an academic, open-label, multicentric, phase II clinical trial evaluating the efficacy and safety of intratumoral injections of ipilimumab and nivolumab combination as neoadjuvant treatment in localized stage III resectable cutaneous or mucosal melanoma patients. Baseline and on-treatment PORTRAIT profiling, as described in the NEOREM Master Protocol (NCT07262489), will be performed using fresh blood and tumor samples. This profiling will reveal the immune status of patients and support biomarker-driven preselection for future trials.

Most cancer treatments are developed without knowing whether the drug's targets are actually present in a patient's tumor or whether the patient is likely to benefit from the treatment. In addition, the immune environment surrounding the tumor changes significantly during the course of the disease, and the body's immune response to cancer tends to become less effective in later stages. Currently, standard blood tests provide only basic information about a patient's immune, inflammatory, and metabolic systems. These tests do not offer a comprehensive picture of how each person's immune system is functioning. Similarly, traditional tests on tumor samples-which require frozen or preserved tissue and take a long time to process-are not fast enough to guide treatment decisions during clinical trials. NEOREM is a "Master Protocol" which includes multiple therapeutic sub-protocols testing new immunotherapy strategies. (Immunotherapy is a type of cancer treatment that helps the immune system fight cancer.) Neoadjuvant immunotherapies are treatments given before surgery. Their goals are to shrink the tumor to make it easier to remove, strengthen the immune system's ability to fight cancer, increase the chances of long-term recovery, and reduce the risk of the cancer returning. This master protocol focuses on cancers that are still localized (have not spread) and aims to personalize treatments based on each patient's individual immuno-biological profile. As a part of this master protocol, a rapid analysis called PORTRAIT-which stands for "Profile in Onco-Immunology for a Rapid Treatment Research Adapted to Immunity and Tumor"-will be performed using fresh blood and tumor samples from each patient. This profiling uses highly sensitive and specific techniques to accurately detect biological markers that can predict how well someone will respond to immunotherapy before surgery. NEOREM's overall goal is to test new treatment strategies and new methods of selecting patients (using the PORTRAIT immune profiling) to improve the effectiveness of current standard treatments for certain types of cancer while also reducing their side effects.

Liver cancer is a highly lethal malignancy and has become increasingly important in western countries. The management of liver cancer is complex. In advanced disease, two combinations of immunotherapies are recommanded as first line (atezolizumab-bevacizumab or durvalumab-tremelimumab). Results in patients with high tumor burden (Portal vein thrombosis Vp3 or Vp4, or tumoral liver involvement \>50%) are less impressive. Innovative combinations are necessary to improve the outcome of patients. Recently, control trials conducted in Asia highlighted the benefit of hepatic arterial infusion chemotherapy, especially in patients with high tumor burden. Studies including a limited number of patients shown that the combination seems feasible. ALICE is a randomized multicentric Phase II/Phase III trial conducted in French medical centers, evaluating the efficacy and safety of durvalumab+tremelimumab with or without Hepatic Arterial Infusion Chemotherapy of the GEMOX regimen (gemcitabine + oxaliplatin), in patients with high tumor burden. Oxaliplatin induce immunogenic cell death, and gemcitabin deplete regulatory immune cells. The GEMOX regimen thus has the potential for a synergic effect with immunotherapy in HCC. The trial will provide an innovative treatment to patients with no alternative for locoregional treatment, and with limited results with actual systemic treatments. It will also be the first trial of Hepatic Arterial infusion for such patients in the western population.

Lynch syndrome is an inherited genetic predisposition that increases the risk of developing several types of cancer, particularly colon and rectal cancers (colorectal cancer), as well as cancer of the uterine lining (endometrial cancer). It affects around 1 in 400 people in Europe. Today, surveillance mainly relies on examinations such as colonoscopy (an examination of the colon using a camera) or gynaecological evaluations, sometimes accompanied by biopsies (the removal of a small tissue sample for microscopic analysis). Although effective, these procedures are invasive and demanding; they can affect quality of life and discourage some individuals from adhering to their recommended surveillance programme. The European project PREDI-LYNCH is exploring an additional pathway that is simpler and better tolerated. This project relies on "liquid biopsies", meaning tests performed on easily collected samples such as blood, urine, stool, and vaginal swabs for women with a uterus. The PREDI-LYNCH study aims to determine whether these non-invasive tests could enable personalised surveillance and potentially increase the interval between more burdensome procedures, while maintaining a high level of medical safety.

CIRCULATE-III is an international, multicenter, open-label, randomized phase III trial designed to use ctDNA as a selection criterion for intensification or de-escalation of adjuvant chemotherapy. Eligible patients are randomly assigned to the following treatment groups: * Patients who test negative for ctDNA receive either capecitabine for 6 months (experimental group) or oxaliplatin + capecitabine for 3 months (standard group). * Patients who test positive for ctDNA receive either FOLFIRINOX for 6 months (experimental group) or FOLFOX for 6 months (standard group). Patient participation in the trial will not exceed 66 months after randomization, including a maximum treatment duration of 6 months and a follow-up period of 60 months.